TRUTAKNA Solution for injection Ref.[116723] Active ingredients:

5.1 Immunosuppression and Increased Risk of Infections

TRUTAKNA suppresses the immune system by reducing antibody production, which may increase the risk of infections. Patients with a chronic infection or recurring infections may have an increased risk of serious infection. In clinical trials, infections were reported in 32% of patients in the TRUTAKNA group compared with 28% of participants in the placebo group [see Adverse Reactions (6.1)].

Before initiating TRUTAKNA, assess patients for active infections. Delay TRUTAKNA administration in patients with active infection until the infection resolves or is adequately treated. During treatment, monitor patients for signs and symptoms of infection. If a serious infection develops, consider interrupting TRUTAKNA until the infection is controlled. The concomitant use of TRUTAKNA and other immune-modulating therapies has not been evaluated. Concomitant use of TRUTAKNA with drugs that affect the immune system, including systemic corticosteroids, may increase the risk of infection.

5.2 Immunosuppression and Immunization Risks

TRUTAKNA may interfere with the immune responses to vaccines and increase the risk of infection from live vaccines. Prior to initiating treatment with TRUTAKNA, complete all age-appropriate immunizations according to current immunization guidelines. Live vaccines are not recommended within 30 days prior to initiation of TRUTAKNA or during treatment with TRUTAKNA as safety of coadministration has not been established.

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Immunosuppression and Increased Risk of Infections [see Warnings and Precautions (5.1)]
• Immunosuppression and Immunization Risks [see Warnings and Precautions (5.2)]

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of TRUTAKNA was evaluated in a randomized, double-blind, placebo-controlled clinical study in 428 adults with IgAN (Origin 3). The median duration of exposure was 34 weeks in the 214 patients treated with TRUTAKNA and 31 weeks in the 214 patients administered placebo [see Clinical Studies (14)].

The most common adverse reactions (reported in ≥5% of patients treated with TRUTAKNA and at a higher incidence than placebo) in patients treated with TRUTAKNA and placebo, respectively, were infections (32% vs. 28%) and local administration reactions (30% vs. 5%). The most common infection was upper respiratory tract infection (12% vs. 9%), and the most common local administration reactions were injection site reaction (19% vs. 2%) and injection site erythema (6% vs. 1%). Most adverse reactions observed in the TRUTAKNA group were mild or moderate in severity and resolved without treatment interruption or discontinuation.

The observed incidence of anti-drug antibodies (ADA) is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of ADA in the studies described below with the incidence of ADA in other studies, including those of TRUTAKNA.

In a pooled analysis of phase 2 and phase 3 clinical data through Week 36 in patients with primary IgAN, 43.2% (60 of 139) of study subjects who were treated with TRUTAKNA once weekly developed ADA. There were no clinically significant effects of ADA on the pharmacokinetics, pharmacodynamics, safety or effectiveness of TRUTAKNA over the treatment duration of 36 weeks in these studies.

Risk Summary

Available data on TRUTAKNA use in pregnant women exposed during clinical trials are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Based on mechanism of action, TRUTAKNA may cause immunosuppression in the in utero-exposed infant [see Warnings and Precautions (5.1 and 5.2), Clinical Pharmacology (12.1) and Clinical Considerations]. There are risks to the mother and infant with untreated IgAN nephropathy in pregnancy (see Clinical Considerations).

In animal reproduction studies, no treatment-related malformations were observed in mice and rabbits at atacicept-vymj exposures approximately up to 12 times and 4 times, respectively, the clinical exposure at the recommended human dose (RHD) (see Data).

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of major birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Pregnant women exposed to TRUTAKNA, or their healthcare providers, should report TRUTAKNA exposure by calling 1-833-633-8372.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

IgAN in pregnancy is associated with adverse maternal outcomes, including increased rates of cesarean section, pregnancy-induced hypertension, pre-eclampsia and preterm delivery, and adverse fetal/neonatal outcomes, including stillbirth and low birth weight.

Fetal/Neonatal Adverse Reactions

Based on mechanism of action, TRUTAKNA may cause immunosuppression in the in utero-exposed infant. The potential clinical impact of TRUTAKNA exposure in infants exposed in utero should be considered.

Data

Animal Data

In pregnant mice, SC administration of atacicept-vymj once every two days (0, 5, 20, and 80 mg/kg) throughout organogenesis from gestation day (GD) 6 to 15 did not result in any adverse effects on embryofetal development at up to 80 mg/kg, approximately 12 times the clinical exposure at the RHD based on area under the concentration curve (AUC).

In pregnant rabbits, SC administration of atacicept-vymj once every two days (0, 5, 20, and 80 mg/kg) throughout organogenesis from GD 6 to 18 resulted in early and late resorptions, reduced number of live fetuses, and decreased mean fetal weight at ≥20 mg/kg, doses that resulted in maternal toxicity (reduced body weight gain). Exposures at these doses were ≥4 times the clinical exposure at the RHD, based on AUC. Embryofetal malformations (enlarged bregmatic fontanella, severe reduction of ossification of parietal or frontal bones, and unossified interparietal bones) were observed at 80 mg/kg (maternally toxic dose), approximately 11 times the clinical exposure at the RHD, based on AUC. No treatment-related malformations were observed at up to 20 mg/kg, approximately 4 times the clinical exposure at the RHD, based on AUC.

In a pre- and post-natal development study in mice, SC administration of atacicept-vymj once every two days (0, 5, 20, or 80 mg/kg) throughout pregnancy and lactation (GD 6 to lactation day 21) did not result in adverse effects on maternal function or development of offspring at up to 80 mg/kg, approximately 12 times the clinical exposure at the RHD based on AUC.

Risk Summary

There are no data regarding the presence of atacicept-vymj in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production/excretion.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for TRUTAKNA and any potential adverse effects on the breastfed child from TRUTAKNA or from the underlying maternal condition.

The safety and effectiveness of TRUTAKNA in pediatric patients have not been established.

Clinical studies of TRUTAKNA did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger adult patients.

No clinically meaningful differences in the pharmacokinetics of TRUTAKNA were observed in patients aged 65 and over compared to younger adult patients.